{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:14:31Z","timestamp":1791850471668,"version":"4.3.4"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Inflammation and metabolic disturbances are key culprits in the pathogenesis of obesity\u2010associated cardiomyopathy. The NLRP3 (nucleotide\u2010binding oligomerization domain\u2010like receptor 3) inflammasome mediates the release of the proinflammatory cytokines IL\u20101\u03b2 (interleukin\u20101\u03b2) and IL\u201018 by activating caspase\u20101, which is strongly implicated in metabolic disturbances. We here sought to determine whether NLRP3 inflammasome inhibition could ameliorate obesity cardiomyopathy and if so, to further explore its underlying mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Male mice were fed a high\u2010fat diet for 24\u2009weeks to induce obesity cardiomyopathy. MCC950 was used to inhibit NLRP3 inflammasome activation. Recombinant adeno\u2010associated virus serotype 9 encoding TXNIP (thioredoxin\u2010interacting protein) under cTnT (cardiac troponin T) promoter and the mitochondrial\u2010targeted antioxidant MitoTEMPO were injected into obese mice to investigate the specific mechanism. To mimic obesity cardiomyopathy in\u00a0vitro, neonatal rat ventricular myocytes transfected with the small interfering RNA against TXNIP were incubated with 400\u2009\u03bcmol palmitic acid for 24\u2009hours. NLRP3 inflammasome was significantly increased in obese hearts. NLRP3 inflammasome inhibition by NLRP3 deletion or MCC950 prevented obesity\u2010induced cardiac systolic and diastolic dysfunction, myocardial hypertrophy and fibrosis, and excessive lipid accumulation in male mice. Conversely, TXNIP overexpression worsened obesity\u2010associated cardiomyopathy. Similarly, MCC950 treatment or TXNIP knockdown reduced palmitic acid\u2010induced NLRP3 inflammasome activation and lipid storage. Mechanistically, abnormal NF\u2010\u03baB (nuclear factor kappa B) pathway activation, increased mitochondrial reactive oxygen species, and elevated TXNIP levels led to excessive NLRP3 inflammasome activation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our study confirms that aberrant NLRP3 inflammasome activation in cardiomyocytes worsens obesity\u2010associated cardiomyopathy and implicates inhibition of NLRP3 inflammasome as a potent therapeutic approach for obesity cardiomyopathy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.035234","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T03:33:27Z","timestamp":1732764807000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Impeding Nucleotide\u2010Binding Oligomerization Domain\u2010Like Receptor 3 Inflammasome Ameliorates Cardiac Remodeling and Dysfunction in Obesity\u2010Associated Cardiomyopathy"],"prefix":"10.1161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7720-6443","authenticated-orcid":false,"given":"Shi\u2010qiang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan PR China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5021-6315","authenticated-orcid":false,"given":"Sai\u2010yang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan PR China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin 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